72 results on '"Tansley S"'
Search Results
2. AB0815 CLINICAL PHENOTYPE AND ANTIBODY CORRELATIONS USING IMMUNOPRECIPITATION IN INDIAN PATIENTS WITH IDIOPATHIC INFLAMMATORY MYOPATHIES FROM THE MYOCITE COHORT
- Author
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Loganathan, A., primary, Rudge, A., additional, Lu, H., additional, Bowler, E., additional, Mcmorrow, F., additional, Ravichandran, N., additional, Anuja, A. K., additional, Agarwal, V., additional, Gupta, L., additional, Mchugh, N., additional, and Tansley, S., additional more...
- Published
- 2023
- Full Text
- View/download PDF
Catalog
3. POS0726 RITUXIMAB VERSUS CYCLOPHOSPHAMIDE FOR ANCA- ASSOCIATED VASCULITIS: A COST ANALYSIS
- Author
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Amor, E., primary, Mulhearn, B., additional, Tillett, W., additional, Cavill, C., additional, and Tansley, S., additional
- Published
- 2023
- Full Text
- View/download PDF
4. POS0753 TIF1-GAMMA IGG2 ISOTYPE IS ASSOCIATED WITH ETHNICITY IN JDM PATIENTS
- Author
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Nguyen, H., primary, Jouen, F., additional, Déchelotte, B., additional, Cordel, N., additional, Gitiaux, C., additional, Bodemer, C., additional, Quartier, P., additional, Belot, A., additional, O’brien, K., additional, Melki, I., additional, Fabien, N., additional, Tansley, S., additional, Wedderburn, L., additional, Boyer, O., additional, and Bader-Meunier, B., additional more...
- Published
- 2023
- Full Text
- View/download PDF
5. OP0160 HLA-DRB1 ASSOCIATIONS WITH AUTOANTIBODY-DEFINED SUBGROUPS IN IDIOPATHIC INFLAMMATORY MYOPATHIES (IIM)
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Leclair, V., primary, Galindo-Feria, A. S., additional, Rothwell, S., additional, Kryštůfková, O., additional, Mann, H., additional, Pyndt Diederichsen, L., additional, Andersson, H., additional, Klein, M., additional, Tansley, S., additional, Mchugh, N., additional, Lamb, J., additional, Vencovský, J., additional, Chinoy, H., additional, Holmqvist, M., additional, Padyukov, L., additional, Lundberg, I. E., additional, and Diaz-Gallo, L. M., additional more...
- Published
- 2022
- Full Text
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6. Histological heterogeneity in a large clinical cohort of juvenile idiopathic inflammatory myopathy: analysis by myositis autoantibody and pathological features
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Yasin, S. A., Schutz, P. W., Deakin, C. T., Sag, E., Varsani, H., Simou, S., Marshall, L. R., Tansley, S. L., McHugh, N. J., Holton, J. L., Wedderburn, L. R., and Jacques, T. S.
- Subjects
Male ,dermatomyositis ,Myositis ,principal component analysis ,Original Articles ,JDM score tool ,Autoantigens ,immune mediated necrotizing myopathy ,polymyositis ,Cohort Studies ,anti‐SRP ,Phenotype ,Child, Preschool ,Humans ,Original Article ,Female ,Child ,Autoantibodies - Abstract
Aim Juvenile idiopathic inflammatory myopathies have been recently reclassified into clinico‐serological subgroups. Myopathological correlates of the subgroups are incompletely understood. Methods We studied muscle biopsies from 101 children with clinically and serologically defined juvenile idiopathic inflammatory myopathies from the UK JDM Cohort and Biomarker Study by applying the international JDM score tool, myopathological review and C5b‐9 complement analysis. Results Autoantibody data were available for 90/101 cases with 18/90 cases positive for anti‐TIF1γ, 15/90 anti‐NXP2, 11/90 anti‐MDA5, 5/90 anti‐Mi2 and 6/90 anti‐PmScl. JDM biopsy severity scores were consistently low in the anti‐MDA5 group, high in the anti‐Mi2 group, and widely distributed in the other groups. Biopsies were classified histologically as perifascicular atrophy (22/101), macrophage‐rich necrosis (6/101), scattered necrosis (2/101), clustered necrosis (2/101), inflammatory fibre invasion (2/101), chronic myopathic change (1/101), diffuse endomysial macrophage infiltrates (40/101) and minimal change (24/101). MDA5 cases segregated with the minimal change group and showed no capillary C5b‐9‐deposition. The Mi2 group displayed high severity scores and a tendency towards sarcolemmal complement deposition. NXP2 and TIF1γ groups showed a variety of pathologies with a high proportion of diffuse endomysial macrophage infiltrates and a high proportion of capillary C5b‐9 deposition. Conclusion We have shown that juvenile idiopathic inflammatory myopathies have a spectrum of histopathological phenotypes and show distinct complement attack complex deposition patterns. Both correlate in some cases with the serological subtypes. Most cases do not show typical histological features associated with dermatomyositis (e.g. perifascicular atrophy). In contrast, more than half show relatively mild histopathological changes. more...
- Published
- 2019
7. Sub-phenotyping of juvenile dermatomyositis: O19
- Author
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Deakin, C. T., Yasin, S. A., Arnold, K., Tansley, S. L., Betteridge, Z. E., McHugh, N. J., Holton, J. L., Jacques, T. S., Pilkington, C., De Iorio, M., and Wedderburn, L. R.
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- 2015
8. Anti-Cytosolic 5'-Nucleotidase 1A Autoantibodies Are Absent in Juvenile Dermatomyositis
- Author
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Rietveld, A., Wienke, J., Visser, E.A., Vree Egberts, W.T.M., Schlumberger, W., Engelen, B.G.M. van, Royen-Kerkhof, A. Van, Lu, H., Wedderburn, L., Saris, C.G.J., Tansley, S., Pruijn, G., Rietveld, A., Wienke, J., Visser, E.A., Vree Egberts, W.T.M., Schlumberger, W., Engelen, B.G.M. van, Royen-Kerkhof, A. Van, Lu, H., Wedderburn, L., Saris, C.G.J., Tansley, S., and Pruijn, G. more...
- Abstract
Contains fulltext : 238504.pdf (Publisher’s version ) (Open Access), OBJECTIVE: To assess anti-cytosolic 5'-nucleotidase 1A (anti-cN-1A) autoantibodies in children with juvenile dermatomyositis (DM) and healthy controls, using 3 different methods of antibody detection, as well as verification of the results in an independent cohort. METHODS: Anti-cN-1A reactivity was assessed in 34 Dutch juvenile DM patients and 20 healthy juvenile controls using the following methods: a commercially available full-length cN-1A enzyme-linked immunosorbent assay (ELISA), a synthetic peptide ELISA, and immunoblotting with a lysate from cN-1A-expressing HEK 293 cells. Sera from juvenile DM patients with active disease and those with disease in remission were analyzed. An independent British cohort of 110 juvenile DM patients and 43 healthy juvenile controls was assessed using an in-house full-length cN-1A ELISA. RESULTS: Anti-cN-1A reactivity was not present in sera from juvenile DM patients or healthy controls when tested with the commercially available full-length cN-1A ELISA or by immunoblotting, in either active disease or disease in remission. Additionally, in the British juvenile DM cohort, anti-cN-1A reactivity was not detected. Three Dutch juvenile DM patients had weakly positive results for 1 of 3 synthetic cN-1A peptides measured by ELISA. CONCLUSION: Juvenile DM patients and young healthy individuals did not show anti-cN-1A reactivity as assessed by different antibody detection techniques. more...
- Published
- 2021
9. OP0281 EXCESS GIANT CELL ARTERITIS CASES ARE ASSOCIATED WITH PEAKS IN COVID-19 PREVALENCE
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Mulhearn, B., primary, Ellis, J., additional, Skeoch, S., additional, Pauling, J., additional, and Tansley, S., additional
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- 2021
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10. POS0288 A KEY TIF1γ EPITOPE MAY FACILITATE THE IDENTIFICATION OF PATIENTS AT HIGHEST RISK OF CANCER ASSOCIATED MYOSITIS
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Riddell, V., primary, Mcmorrow, F., additional, Oldroyd, A., additional, Deakin, C., additional, Lamb, J., additional, Chinoy, H., additional, Wedderburn, L., additional, Bagby, S., additional, Mchugh, N., additional, and Tansley, S., additional more...
- Published
- 2021
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11. CD38 as a prognostic marker in chronic lymphocytic leukaemia at a single New Zealand centre: patient survival in comparison to age- and sex-matched population data
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Hock, B. D., McKenzie, J. L., McArthur, L., Tansley, S., Taylor, K. G., and Fernyhough, L. J.
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- 2010
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12. Genome-wide association reveals contribution of MRAS to painful temporomandibular disorder in males
- Author
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Smith, S. B. (Shad B.), Parisien, M. (Marc), Bair, E. (Eric), Belfer, I. (Inna), Chabot-Dore, A.-J. (Anne-Julie), Gris, P. (Pavel), Khoury, S. (Samar), Tansley, S. (Shannon), Torosyan, Y. (Yelizaveta), Zaykin, D. (Dmitri), Bernhardt, O. (Olaf), Serrano, P. d. (Priscila de Oliveira), Gracely, R. (Richard), Jain, D. (Deepti), Järvelin, M.-R. (Marjo-Riitta), Kaste, L. (Linda), Kerr, K. (Kathleen), Kocher, T. (Thomas), Lähdesmaki, R. (Raija), Laniado, N. (Nadia), Laurie, C. (Cathy), Laurie, C. (Cecelia), Männikko, M. (Minna), Meloto, C. (Carolina), Nackley, A. (Andrea), Nelson, S. (Sarah), Pesonen, P. (Paula), Ribeiro-Dasilva, M. (Margarete), Rizzatti-Barbosa, C. (Celia), Sanders, A. (Anne), Schwahn, C. (Christian), Sipilä, K. (Kirsi), Sofer, T. (Tamar), Teumer, A. (Alexander), Mogil, J. (Jeffrey), Fillingim, R. (Roger), Greenspan, J. (Joel), Ohrbach, R. (Richard), Slade, G. (Gary), Maixner, W. (William), Diatchenko, L. (Luda), Smith, S. B. (Shad B.), Parisien, M. (Marc), Bair, E. (Eric), Belfer, I. (Inna), Chabot-Dore, A.-J. (Anne-Julie), Gris, P. (Pavel), Khoury, S. (Samar), Tansley, S. (Shannon), Torosyan, Y. (Yelizaveta), Zaykin, D. (Dmitri), Bernhardt, O. (Olaf), Serrano, P. d. (Priscila de Oliveira), Gracely, R. (Richard), Jain, D. (Deepti), Järvelin, M.-R. (Marjo-Riitta), Kaste, L. (Linda), Kerr, K. (Kathleen), Kocher, T. (Thomas), Lähdesmaki, R. (Raija), Laniado, N. (Nadia), Laurie, C. (Cathy), Laurie, C. (Cecelia), Männikko, M. (Minna), Meloto, C. (Carolina), Nackley, A. (Andrea), Nelson, S. (Sarah), Pesonen, P. (Paula), Ribeiro-Dasilva, M. (Margarete), Rizzatti-Barbosa, C. (Celia), Sanders, A. (Anne), Schwahn, C. (Christian), Sipilä, K. (Kirsi), Sofer, T. (Tamar), Teumer, A. (Alexander), Mogil, J. (Jeffrey), Fillingim, R. (Roger), Greenspan, J. (Joel), Ohrbach, R. (Richard), Slade, G. (Gary), Maixner, W. (William), and Diatchenko, L. (Luda) more...
- Abstract
Painful temporomandibular disorders (TMDs) are the leading cause of chronic orofacial pain, but its underlying molecular mechanisms remain obscure. Although many environmental factors have been associated with higher risk of developing painful TMD, family and twin studies support a heritable genetic component as well. We performed a genome-wide association study assuming an additive genetic model of TMD in a discovery cohort of 999 cases and 2031 TMD-free controls from the Orofacial Pain: Prospective Evaluation and Risk Assessment (OPPERA) study. Using logistic models adjusted for sex, age, enrollment site, and race, we identified 3 distinct loci that were significant in combined or sex-segregated analyses. A single-nucleotide polymorphism on chromosome 3 (rs13078961) was significantly associated with TMD in males only (odds ratio = 2.9, 95% confidence interval: 2.02–4.27, P = 2.2 × 10⁻⁸). This association was nominally replicated in a meta-analysis of 7 independent orofacial pain cohorts including 160,194 participants (odds ratio = 1.16, 95% confidence interval: 1.0–1.35, P = 2.3 × 10⁻²). Functional analysis in human dorsal root ganglia and blood indicated this variant is an expression quantitative trait locus, with the minor allele associated with decreased expression of the nearby muscle RAS oncogene homolog (MRAS) gene (beta = −0.51, P = 2.43 × 10⁻⁵). Male mice, but not female mice, with a null mutation of Mras displayed persistent mechanical allodynia in a model of inflammatory pain. Genetic and behavioral evidence support a novel mechanism by which genetically determined MRAS expression moderates the resiliency to chronic pain. This effect is male-specific and may contribute to the lower rates of painful TMD in men. more...
- Published
- 2019
13. Effective induction therapy for anti-SRP associated myositis in childhood:A small case series and review of the literature
- Author
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Binns, E L, Moraitis, Elena, Maillard, S, Tansley, S, McHugh, N, Jacques, Thomas S, Wedderburn, L R, Pilkington, Clarissa, Yasin, S A, and Nistala, Kiran
- Subjects
Journal Article - Abstract
BACKGROUND: Anti-Signal Recognition Particle associated myopathy is a clinically and histopathologically distinct subgroup of Juvenile Idiopathic Inflammatory Myositis, which is under-recognised in children and fails to respond to conventional first line therapies. We present three cases where remission was successfully induced using combination therapy with intensive rehabilitation.CASE PRESENTATIONS: Three new patients are reported. All 3 cases presented with profound, rapid-onset, proximal myopathy and markedly raised CK, but no rash. Histology revealed a destructive myopathy characterized by scattered atrophic and necrotic fibres with little or no inflammatory infiltrate. All 3 patients responded to induction with cyclophosphamide, IVIG and rituximab, in conjunction with intensive physiotherapy and methotrexate as the maintenance agent. Our patients regained near-normal strength (MMT > 70/80), in contrast with the current literature where >50% of cases reported severe residual weakness. A literature search on paediatric anti-SRP myositis was performed to June 2016; PubMed was screened using a combination of the following terms: signal recognition particle, autoantibodies, antibodies, myositis, muscular diseases, skeletal muscle, childhood, paediatric, juvenile. Articles in a foreign language were excluded. Nine case studies were found.CONCLUSION: This paper supports the hypothesis that anti-SRP myositis is distinct from other JIIM. It is an important differential to JDM and should be considered where there is severe weakness without rash or if highly elevated muscle enzymes (CK > 10,000 U/l) are found. Early identification is essential to initiate aggressive medical and physical therapy. Greater international collaboration and long-term follow-up data is needed to establish the most effective treatment strategy for this rare group of patients. more...
- Published
- 2017
- Full Text
- View/download PDF
14. Expression of myxovirus‐resistance protein A: a possible marker of muscle disease activity and autoantibody specificities in juvenile dermatomyositis
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Soponkanaporn, S., primary, Deakin, C. T., additional, Schutz, P. W., additional, Marshall, L. R., additional, Yasin, S. A., additional, Johnson, C. M., additional, Sag, E., additional, Tansley, S. L., additional, McHugh, N. J., additional, Wedderburn, L. R., additional, and Jacques, T. S., additional more...
- Published
- 2018
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- View/download PDF
15. AB1222 Comparison of quantitative mri fat-fraction measurement in sij joint on different scanner platforms
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Bainbridge, A., primary, Bray, T., additional, Jones, J., additional, Tansley, S., additional, Fulstow, N., additional, Sengupta, R., additional, and Hall-Craggs, M., additional
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- 2018
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16. Extracellular matrix mediated plasticity in neuropathic pain
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Tansley, S., primary, Samoshkin, A., additional, Parisien, M., additional, Piltonen, M., additional, Martin, L., additional, Mogil, J., additional, Diatchenko, L., additional, and Khoutorsky, A., additional more...
- Published
- 2018
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17. Developing standardised treatment for adults with myositis and different phenotypes: an international survey of current prescribing preferences
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Tansley S, Shaddick G, Christopher-Stine L, Sharp C, Dourmishev L, Maurer B, Hector Chinoy, McHugh N, University of Zurich, and Tansley, Sarah
- Subjects
Health Knowledge, Attitudes, Practice ,2403 Immunology ,Consensus ,Myositis ,Attitude of Health Personnel ,2745 Rheumatology ,10051 Rheumatology Clinic and Institute of Physical Medicine ,610 Medicine & health ,Drug Prescriptions ,Phenotype ,Rheumatology ,Health Care Surveys ,2723 Immunology and Allergy ,Humans ,Practice Patterns, Physicians' ,Rheumatologists ,Immunosuppressive Agents - Abstract
The evidence base for treatment of the idiopathic inflammatory myopathies is extremely limited. The rarity and heterogeneity of these diseases has hampered the development of good quality clinical trials and while a range of immunomodulatory treatments are commonly used in clinical practice, as yet there are no clear guidelines directing their use. We aimed to establish current prescribing regimens used to treat adults with myositis internationally.An electronic survey based on different clinical scenarios was distributed internationally to clinicians involved in the treatment of patients with myositis. Participants were asked to select their first-line treatment preferences in each situation. A multinomial regression analysis was used to assess the influence of clinical scenario, respondent expertise and country of origin on first-line treatment choice.107 survey responses were received. 57% of respondents considered themselves an expert in myositis and the majority of respondents were rheumatologists although responses from other specialities were also received. Pharmacological treatment with steroids and additional immunotherapy was the preference in most scenarios. First-line immunosuppressant choice was significantly influenced by the clinical scenario, the expertise of the treating physician and country of practice. Azathioprine, methotrexate and mycophenolate mofetil were the most commonly chosen agents.In the absence of available evidence, clinical experience and expert consensus often forms the basis of treatment guidelines. These results suggest that an international consensus approach would be possible in myositis and would overcome an urgent, yet unmet need for patients suffering with this difficult disease. more...
- Published
- 2016
18. CLINICAL PHENOTYPE AND ANTIBODY CORRELATIONS USING IMMUNOPRECIPITATION IN INDIAN PATIENTS WITH IDIOPATHIC INFLAMMATORY MYOPATHIES FROM THE MYOCITE COHORT.
- Author
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Loganathan, A., Rudge, A., Lu, H., Bowler, E., Mcmorrow, F., Ravichandran, N., Anuja, A. K., Agarwal, V., Gupta, L., Mchugh, N., and Tansley, S.
- Published
- 2023
- Full Text
- View/download PDF
19. TIF1-GAMMA IGG2 ISOTYPE IS ASSOCIATED WITH ETHNICITY IN JDM PATIENTS.
- Author
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Nguyen, H., Jouen, F., Déchelotte, B., Cordel, N., Gitiaux, C., Bodemer, C., Quartier, P., Belot, A., O'brien, K., Melki, I., Fabien, N., Tansley, S., Wedderburn, L., Boyer, O., and Bader-Meunier, B.
- Published
- 2023
- Full Text
- View/download PDF
20. Expression of myxovirus‐resistance protein A: a possible marker of muscle disease activity and autoantibody specificities in juvenile dermatomyositis.
- Author
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Soponkanaporn, S., Deakin, C. T., Schutz, P. W., Marshall, L. R., Yasin, S. A., Johnson, C. M., Sag, E., Tansley, S. L., McHugh, N. J., Wedderburn, L. R., and Jacques, T. S.
- Subjects
ORTHOMYXOVIRUSES ,DERMATOMYOSITIS ,AUTOANTIBODIES ,BIOMARKERS ,GENE expression ,MUSCLE diseases - Abstract
Aims: To evaluate the relationship between expression of myxovirus‐resistance protein A (MxA) protein on muscle biopsies by immunohistochemistry and disease activity in juvenile dermatomyositis (JDM) patients. Also, another aim was to investigate whether the expression of MxA is related with myositis‐specific autoantibodies (MSA) status in JDM patients. Methods: 103 patients (median aged 6.3, interquartile range 0.5–15.9) enrolled in the Juvenile Dermatomyositis Cohort and Biomarker Study (JDCBS). Muscle biopsies were stained with MxA and scored. Clinical data at initial presentation were collected and autoantibodies were analysed. Multiple linear regression analysis was performed to estimate the association between MxA expression on muscle fibres and muscle disease activity, and MSA status. Results: Expression of MxA protein on JDM samples was identified in 61.2%. There was a significant association between MxA scores and Childhood Myositis Assessment Scale (CMAS) (P = 0.002), and Manual Muscle Testing of Eight Muscles (MMT8) (P = 0.026). CMAS and MMT8 scores were significantly lower in the group of patients with strong MxA expression. MxA scores differed according to MSA subgroups (P = 0.002). Patients with positive nuclear matrix protein 2 autoantibodies had strong MxA expression, whereas anti‐melanoma differentiation‐associated gene 5 positive patients had no or weak MxA expression. Conclusions: This study reveals the significant association between level of MxA expression on muscle fibres and clinical measures of muscular disease activity in JDM patients and MSA status. This confirms type I interferonopathies in muscle fibres of JDM patients which could help with improving treatment outcome in JDM patients and underscoring the distinct pathophysiological pathways in different MSA status. [ABSTRACT FROM AUTHOR] more...
- Published
- 2019
- Full Text
- View/download PDF
21. (154) - Extracellular matrix mediated plasticity in neuropathic pain
- Author
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Tansley, S., Samoshkin, A., Parisien, M., Piltonen, M., Martin, L., Mogil, J., Diatchenko, L., and Khoutorsky, A.
- Published
- 2018
- Full Text
- View/download PDF
22. Effective induction therapy for anti-SRP associated myositis in childhood: A small case series and review of the literature.
- Author
-
Binns, E. L., Moraitis, E., Maillard, S., Tansley, S., McHugh, N., Jacques, T. S., Wedderburn, L. R., Pilkington, C., Yasin, S. A., and Nistala, K.
- Subjects
MYOSITIS ,CYCLOPHOSPHAMIDE ,METHOTREXATE ,PHYSIOLOGICAL therapeutics ,THERAPEUTICS - Abstract
Background: Anti-Signal Recognition Particle associated myopathy is a clinically and histopathologically distinct subgroup of Juvenile Idiopathic Inflammatory Myositis, which is under-recognised in children and fails to respond to conventional first line therapies. We present three cases where remission was successfully induced using combination therapy with intensive rehabilitation. Case presentations: Three new patients are reported. All 3 cases presented with profound, rapid-onset, proximal myopathy and markedly raised CK, but no rash. Histology revealed a destructive myopathy characterized by scattered atrophic and necrotic fibres with little or no inflammatory infiltrate. All 3 patients responded to induction with cyclophosphamide, IVIG and rituximab, in conjunction with intensive physiotherapy and methotrexate as the maintenance agent. Our patients regained near-normal strength (MMT > 70/80), in contrast with the current literature where >50% of cases reported severe residual weakness. A literature search on paediatric anti-SRP myositis was performed to June 2016; PubMed was screened using a combination of the following terms: signal recognition particle, autoantibodies, antibodies, myositis, muscular diseases, skeletal muscle, childhood, paediatric, juvenile. Articles in a foreign language were excluded. Nine case studies were found. Conclusion: This paper supports the hypothesis that anti-SRP myositis is distinct from other JIIM. It is an important differential to JDM and should be considered where there is severe weakness without rash or if highly elevated muscle enzymes (CK > 10,000 U/l) are found. Early identification is essential to initiate aggressive medical and physical therapy. Greater international collaboration and long-term follow-up data is needed to establish the most effective treatment strategy for this rare group of patients. [ABSTRACT FROM AUTHOR] more...
- Published
- 2017
- Full Text
- View/download PDF
23. RITUXIMAB VERSUS CYCLOPHOSPHAMIDE FOR ANCA-ASSOCIATED VASCULITIS: A COST ANALYSIS.
- Author
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Amor, E., Mulhearn, B., Tillett, W., Cavill, C., and Tansley, S.
- Published
- 2023
- Full Text
- View/download PDF
24. The future of data policy
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Hey, T, Tolle, K, Tansley, S, Fitzgerald, Anne, Fitzgerald, Brian, Pappalardo, Kylie, Hey, T, Tolle, K, Tansley, S, Fitzgerald, Anne, Fitzgerald, Brian, and Pappalardo, Kylie
- Published
- 2009
25. Oral Abstracts 3: Adolescent and Young Adult * O13. Hypermobility is a Risk Factor for Musculoskeletal Pain in Adolescence: Findings From a Prospective Cohort Study
- Author
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Tobias, J., primary, Deere, K., additional, Palmer, S., additional, Clark, E., additional, Clinch, J., additional, Fikree, A., additional, Aktar, R., additional, Wellstead, G., additional, Knowles, C., additional, Grahame, R., additional, Aziz, Q., additional, Amaral, B., additional, Murphy, G., additional, Ioannou, Y., additional, Isenberg, D. A., additional, Tansley, S. L., additional, Betteridge, Z. E., additional, Gunawardena, H., additional, Shaddick, G., additional, Varsani, H., additional, Wedderburn, L., additional, McHugh, N., additional, De Benedetti, F., additional, Ruperto, N., additional, Espada, G., additional, Gerloni, V., additional, Flato, B., additional, Horneff, G., additional, Myones, B. L., additional, Onel, K., additional, Frane, J., additional, Kenwright, A., additional, Lipman, T. H., additional, Bharucha, K. N., additional, Martini, A., additional, Lovell, D. J., additional, Baildam, E., additional, Brunner, H., additional, Zuber, Z., additional, Keane, C., additional, Harari, O., additional, Cuttica, R. J., additional, Keltsev, V., additional, Xavier, R., additional, Penades, I. C., additional, Nikishina, I., additional, Rubio-Perez, N., additional, Alekseeva, E., additional, Chasnyk, V., additional, Chavez, J., additional, Opoka-Winiarska, V., additional, Quartier, P., additional, Silva, C. A., additional, Silverman, E. D., additional, Spindler, A., additional, Hendry, G. J., additional, Watt, G. F., additional, Brandon, M., additional, Friel, L., additional, Turner, D., additional, Lorgelly, P. K., additional, Gardner-Medwin, J., additional, Sturrock, R. D., additional, Woodburn, J., additional, Firth, J., additional, Waxman, R., additional, Law, G., additional, Siddle, H., additional, Nelson, A. E., additional, Helliwell, P., additional, Otter, S., additional, Butters, V., additional, Loughrey, L., additional, Alcacer-Pitarch, B., additional, Tranter, J., additional, Davies, S., additional, Hryniw, R., additional, Lewis, S., additional, Baker, L., additional, Dures, E., additional, Hewlett, S., additional, Ambler, N., additional, Clarke, J., additional, Gooberman-Hill, R., additional, Jenkins, R., additional, Wilkie, R., additional, Bucknall, M., additional, Jordan, K., additional, McBeth, J., additional, Norton, S., additional, Walsh, D., additional, Kiely, P., additional, Williams, R., additional, Young, A., additional, Harkess, J. E., additional, McAlarey, K., additional, Chesterton, L., additional, van der Windt, D. A., additional, Sim, J., additional, Lewis, M., additional, Mallen, C. D., additional, Mason, E., additional, Hay, E., additional, Clarson, L. E., additional, Hider, S. L., additional, Belcher, J., additional, Heneghan, C., additional, Roddy, E., additional, Gibson, J., additional, Whiteford, S., additional, Williamson, E., additional, Beatty, S., additional, Hamilton-Dyer, N., additional, Healey, E. L., additional, Ryan, S., additional, McHugh, G. A., additional, Main, C. J., additional, Porcheret, M., additional, Nio Ong, B., additional, Pushpa-Rajah, A., additional, Dziedzic, K. S., additional, MacRae, C. S., additional, Shortland, A., additional, Lewis, J., additional, Morrissey, M., additional, Critchley, D., additional, Muller, S., additional, Helliwell, T., additional, Cole, Z., additional, Parsons, C., additional, Crozier, S., additional, Robinson, S., additional, Taylor, P., additional, Inskip, H., additional, Godfrey, K., additional, Dennison, E., additional, Harvey, N. C., additional, Cooper, C., additional, Prieto Alhambra, D., additional, Lalmohamed, A., additional, Abrahamsen, B., additional, Arden, N., additional, de Boer, A., additional, Vestergaard, P., additional, de Vries, F., additional, Kendal, A., additional, Carr, A., additional, Prieto-Alhambra, D., additional, Judge, A., additional, Chapurlat, R., additional, Bellamy, N., additional, Czerwinski, E., additional, Pierre Devogelaer, J., additional, March, L., additional, Pavelka, K., additional, Reginster, J.-Y., additional, Kiran, A., additional, Javaid, M. K., additional, Sundy, J. S., additional, Baraf, H. S., additional, Becker, M., additional, Treadwell, E. L., additional, Yood, R., additional, and Ottery, F. D., additional more...
- Published
- 2013
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26. Evaluation of FRAX as a screening tool to predict or exclude the presence of osteoporosis in clinical practice
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Tansley, S., primary, Hannan, J., additional, Millar, C., additional, and Ralston, S., additional
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- 2010
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27. CD38 as a prognostic marker in chronic lymphocytic leukaemia at a single New Zealand centre: patient survival in comparison to age- and sex-matched population data
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Hock, B. D., primary, McKenzie, J. L., additional, McArthur, L., additional, Tansley, S., additional, Taylor, K. G., additional, and Fernyhough, L. J., additional
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- 2009
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28. Environmental Monitoring 2.0.
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Michel, S., Salehi, A., Liqian Luo, Dawes, N., Aberer, K., Barrenetxea, G., Bavay, M., Kansal, A., Kumar, K.A., Nath, S., Parlange, M., Tansley, S., van Ingen, C., Feng Zhao, and Yongluan Zhou
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- 2009
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29. MELIANTHACEAE
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Tansley, S. A., primary and Schelpe, E. A. C. L. E., additional
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- 1984
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30. Trends in Embedded Systems--A Microsoft Perspective.
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Tansley, S.
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- 2007
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31. TIF1-gamma IgG2 isotype is not associated with malignancy in juvenile dermatomyositis patients.
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Nguyen HD, Jouen F, Déchelotte B, Cordel N, Gitiaux C, Bodemer C, Quartier P, Belot A, O'Brien K, Cancemi D, Melki I, Fabien N, Tansley S, Boyer O, Wedderburn LR, and Bader-Meunier B
- Subjects
- Humans, Female, Child, Male, Neoplasms immunology, Transcription Factors immunology, Transcription Factors genetics, Adolescent, Child, Preschool, Dermatomyositis immunology, Immunoglobulin G immunology, Immunoglobulin G blood
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- 2024
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32. Assessing the sensitivity and specificity of myositis-specific and associated autoantibodies: a sub-study from the MyoCite cohort.
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Loganathan A, Gupta L, Rudge A, Lu H, Bowler E, McMorrow F, Naveen R, Anuja AK, Agarwal V, McHugh N, and Tansley S
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- Humans, Male, Female, Adult, Middle Aged, Interferon-Induced Helicase, IFIH1 immunology, Immunoprecipitation, Biomarkers blood, Adolescent, Immunoassay methods, Child, Cohort Studies, Young Adult, Prospective Studies, Adenosine Triphosphatases, DNA-Binding Proteins, Transcription Factors, Autoantibodies blood, Autoantibodies immunology, Myositis immunology, Myositis blood, Myositis diagnosis, Sensitivity and Specificity
- Abstract
Objectives: Myositis-specific and associated autoantibodies are important biomarkers in routine clinical use. We assessed local testing performance for myositis autoantibodies by comparing line immunoassay (LIA) to protein radio-immunoprecipitation and identifying clinical characteristics associated with each myositis autoantibody in the MyoCite cohort., Methods: Serum samples from patients within the MyoCite cohort, a well-characterized retro-prospective dataset of adult and juvenile idiopathic inflammatory myopathy (IIM) patients in Lucknow, India (2017-2020), underwent LIA at Sanjay Gandhi Postgraduate Institute of Medical Science (SGPGIMS), Lucknow. Immunoprecipitation of 147 IIM patients' serum samples (125 adult-onset, 22 juvenile-onset) was conducted at the University of Bath, with researchers blind to LIA results. LIA performance was assessed against immunoprecipitation as the reference standard, measuring sensitivity, specificity and inter-rater agreement. Univariate and multivariate logistic regression determined clinical associations for specific myositis-specific autoantibodies., Results: Immunoprecipitation identified myositis autoantibodies in 56.5% (n = 83) of patient samples, with anti-Jo1 (n = 16; 10.9%) as the most common, followed by anti-MDA5 (n = 14, 9.5%). While LIA showed good agreement for anti-Jo1, anti-PL7 and anti-PL12 (Cohen's κ 0.79, 0.83 and 1, respectively), poor agreement was observed in other subgroups, notably anti-TIF1γ (Cohen's κ 0.21). Strongly positive samples, especially in myositis-specific autoantibodies, correlated more with immunoprecipitation results. Overall, 59 (40.1%) samples exhibited non-congruence on LIA and immunoprecipitation, and κ values for LIAs for anti-TIF1γ, anti-Ku, anti-PmScl, anti-Mi2 and anti-SAE ranged between 0.21 and 0.60., Conclusion: While LIA reliably detected anti-Jo1, anti-PL7, anti-PL12, anti-MDA5 and anti-NXP-2, it also displayed false positives and negatives. Its effectiveness in detecting other autoantibodies, such as anti-TIF1γ, was poor., (© Crown copyright 2024.) more...
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- 2024
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33. Agreement between local and central anti-synthetase antibodies detection: results from the Classification Criteria of Anti-Synthetase Syndrome project biobank.
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Loganathan A, Zanframundo G, Yoshida A, Faghihi-Kashani S, Bauer Ventura I, Dourado E, Bozan F, Sambataro G, Yamano Y, Bae SS, Lim D, Ceribelli A, Isailovic N, Selmi C, Fertig N, Bravi E, Kaneko Y, Saraiva AP, Jovani V, Bachiller-Corral J, Cifrian J, Mera-Varela A, Moghadam-Kia S, Wolff V, Campagne J, Meyer A, Giannini M, Triantafyllias K, Knitza J, Gupta L, Molad Y, Iannone F, Cavazzana I, Piga M, De Luca G, Tansley S, Bozzalla-Cassione E, Bonella F, Corte TJ, Doyle TJ, Fiorentino D, Gonzalez-Gay MA, Hudson M, Kuwana M, Lundberg IE, Mammen AL, McHugh NJ, Miller FW, Montecucco C, Oddis CV, Rojas-Serrano J, Schmidt J, Scirè CA, Selva-O'Callaghan A, Werth VP, Alpini C, Bozzini S, Cavagna L, and Aggarwal R more...
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- Humans, Ligases, Reproducibility of Results, Biological Specimen Banks, Autoantibodies, Amino Acyl-tRNA Synthetases, Myositis diagnosis
- Abstract
Objectives: The CLASS (Classification Criteria of Anti-Synthetase Syndrome) project is a large international multicentre study that aims to create the first data-driven anti-synthetase syndrome (ASSD) classification criteria. Identifying anti-aminoacyl tRNA synthetase antibodies (anti-ARS) is crucial for diagnosis, and several commercial immunoassays are now available for this purpose. However, using these assays risks yielding false-positive or false-negative results, potentially leading to misdiagnosis. The established reference standard for detecting anti-ARS is immunoprecipitation (IP), typically employed in research rather than routine autoantibody testing. We gathered samples from participating centers and results from local anti-ARS testing. As an "ad-interim" study within the CLASS project, we aimed to assess how local immunoassays perform in real-world settings compared to our central definition of anti-ARS positivity., Methods: We collected 787 serum samples from participating centres for the CLASS project and their local anti-ARS test results. These samples underwent initial central testing using RNA-IP. Following this, the specificity of ARS was reconfirmed centrally through ELISA, line-blot assay (LIA), and, in cases of conflicting results, protein-IP. The sensitivity, specificity, positive likelihood ratio and positive and negative predictive values were evaluated. We also calculated the inter-rater agreement between central and local results using a weighted κ co-efficient., Results: Our analysis demonstrates that local, real-world detection of anti-Jo1 is reliable with high sensitivity and specificity with a very good level of agreement with our central definition of anti-Jo1 antibody positivity. However, the agreement between local immunoassay and central determination of anti-non-Jo1 antibodies varied, especially among results obtained using local LIA, ELISA and "other" methods., Conclusions: Our study evaluates the performance of real-world identification of anti-synthetase antibodies in a large cohort of multi-national patients with ASSD and controls. Our analysis reinforces the reliability of real-world anti-Jo1 detection methods. In contrast, challenges persist for anti-non-Jo1 identification, particularly anti-PL7 and rarer antibodies such as anti-OJ/KS. Clinicians should exercise caution when interpreting anti-synthetase antibodies, especially when commercial immunoassays test positive for non-anti-Jo1 antibodies. more...
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- 2024
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34. Relapse after cessation of weekly tocilizumab for giant cell arteritis: a multicentre service evaluation in England.
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Quick V, Abusalameh M, Ahmed S, Alkoky H, Bukhari M, Carter S, Coath FL, Davidson B, Doddamani P, Dubey S, Ducker G, Griffiths B, Gullick N, Heaney J, Holloway A, Htut EEP, Hughes M, Irvine H, Kinder A, Kurshid A, Lim J, Ludwig DR, Malik M, Mercer L, Mulhearn B, Nair JR, Patel R, Robson J, Saha P, Tansley S, and Mackie SL more...
- Abstract
Objectives: The National Health Service in England funds 12 months of weekly subcutaneous tocilizumab (qwTCZ) for patients with relapsing or refractory giant cell arteritis (GCA). During the COVID-19 pandemic, some patients were allowed longer treatment. We sought to describe what happened to patients after cessation of qwTCZ., Methods: Multicentre service evaluation of relapse after stopping qwTCZ for GCA. The log-rank test was used to identify significant differences in time to relapse., Results: 336 GCA patients were analysed from 40 centres, treated with qwTCZ for a median (interquartile range, IQR) of 12 (12-17) months. At time of stopping qwTCZ, median (IQR) prednisolone dose was 2 (0-5) mg/day. By 6, 12 and 24 months after stopping qwTCZ, 21.4%, 35.4% and 48.6% respectively had relapsed, requiring an increase in prednisolone dose to a median (IQR) of 20 (10-40) mg/day. 33.6% of relapsers had a major relapse as defined by EULAR. Time to relapse was shorter in those that had previously also relapsed during qwTCZ treatment (P = 0.0017); in those not in remission at qwTCZ cessation (P = 0.0036); and in those with large vessel involvement on imaging (P = 0.0296). Age ≥65, gender, GCA-related sight loss, qwTCZ treatment duration, TCZ taper, prednisolone dosing, and conventional synthetic DMARD use were not associated with time to relapse., Conclusion: Up to half our patients with GCA relapsed after stopping qwTCZ, often requiring a substantial increase in prednisolone dose. One third of relapsers had a major relapse. Extended use of TCZ or repeat treatment for relapse should be considered for these patients., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.) more...
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- 2023
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35. Distinct HLA associations with autoantibody-defined subgroups in idiopathic inflammatory myopathies.
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Leclair V, Galindo-Feria AS, Rothwell S, Kryštůfková O, Zargar SS, Mann H, Diederichsen LP, Andersson H, Klein M, Tansley S, Rönnblom L, Lindblad-Toh K, Syvänen AC, Wahren-Herlenius M, Sandling JK, McHugh N, Lamb JA, Vencovský J, Chinoy H, Holmqvist M, Bianchi M, Padyukov L, Lundberg IE, and Diaz-Gallo LM more...
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- Humans, Alleles, Genetic Predisposition to Disease, Haplotypes, HLA-DRB1 Chains genetics, Phenotype, Autoantibodies genetics, Myositis genetics, Myositis immunology
- Abstract
Background: In patients with idiopathic inflammatory myopathies (IIM), autoantibodies are associated with specific clinical phenotypes suggesting a pathogenic role of adaptive immunity. We explored if autoantibody profiles are associated with specific HLA genetic variants and clinical manifestations in IIM., Methods: We included 1348 IIM patients and determined the occurrence of 14 myositis-specific or -associated autoantibodies. We used unsupervised cluster analysis to identify autoantibody-defined subgroups and logistic regression to estimate associations with clinical manifestations, HLA-DRB1, HLA-DQA1, HLA-DQB1 alleles, and amino acids imputed from genetic information of HLA class II and I molecules., Findings: We identified eight subgroups with the following dominant autoantibodies: anti-Ro52, -U1RNP, -PM/Scl, -Mi2, -Jo1, -Jo1/Ro52, -TIF1γ or negative for all analysed autoantibodies. Associations with HLA-DRB1∗11, HLA-DRB1∗15, HLA-DQA1∗03, and HLA-DQB1∗03 were present in the anti-U1RNP-dominated subgroup. HLA-DRB1∗03, HLA-DQA1∗05, and HLA-DQB1∗02 alleles were overrepresented in the anti-PM/Scl and anti-Jo1/Ro52-dominated subgroups. HLA-DRB1∗16, HLA-DRB1∗07 alleles were most frequent in anti-Mi2 and HLA-DRB1∗01 and HLA-DRB1∗07 alleles in the anti-TIF1γ subgroup. The HLA-DRB1∗13, HLA-DQA1∗01 and HLA-DQB1∗06 alleles were overrepresented in the negative subgroup. Significant signals from variations in class I molecules were detected in the subgroups dominated by anti-Mi2, anti-Jo1/Ro52, anti-TIF1γ, and the negative subgroup., Interpretation: Distinct HLA class II and I associations were observed for almost all autoantibody-defined subgroups. The associations support autoantibody profiles use for classifying IIM which would likely reflect underlying pathogenic mechanisms better than classifications based on clinical symptoms and/or histopathological features., Funding: See a detailed list of funding bodies in the Acknowledgements section at the end of the manuscript., Competing Interests: Declaration of interests Professor Lundberg has received consulting fees from Corbus Pharmaceuticals, Inc and research grants from Astra Zeneca and has been serving on the advisory board for Astra Zeneca, Bristol Myers Squibb, EMD Serono Research & Development Institute, Argenx, Octapharma, Kezaar, Orphazyme, Pfizer and Janssen and has stock shares in Roche and Novartis. Professor Vencovský has received speaker fees from Abbvie, Biogen, Boehringer, Eli Lilly, Gilead, MSD, Novartis, Pfizer, Roche, Sanofi, UCB, Werfen; and has received consulting fees from Abbvie, Argenx, Boehringer, Eli Lilly, Gilead, Octapharma, Pfizer, UCB. Professor Chinoy has received personal compensation for activities with Novartis, UCB, Eli Lilly, Biogen, Orphazyme, Astra Zeneca, Pfizer, Kezar Life Sciences, Galapagos, Argenx, GSK as a speaker, advisory board member or consultancy; grants via The University of Manchester from Eli Lilly and UCB; travel support from Abbvie and Janssen. Dr Mann has received honoraria from Abbvie, Biogen, BMS, Eli Lilly, MSD, Janssen, Novartis, UCB, Pfizer, SOBI and travel support by Abbvie. Dr Tansley received payment from Boehringer Ingelheim as a speaker. Dr Rönnblom received support from The Swedish Research Council (2018–02399), Reumatikerförbundet (R-939716) and GV:80 (FAI-2020-0658) foundation. Dr Holmqvist received support from The Swedish Research Council, Stockholm Regional Council (ALF), Reumatikerförbundet, Konung Gustaf V:80 year foundation, The Swedish Cancer Association and was a member of Medical Advisory Board of The Myositis Association. Dr Lamb received support from the Medical Research Council UK and Myositis UK. Other authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.) more...
- Published
- 2023
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36. Incidence of giant cell arteritis is associated with COVID-19 prevalence: A population-level retrospective study.
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Mulhearn B, Ellis J, Skeoch S, Pauling J, and Tansley S
- Abstract
Background: Following the first wave of the COVID-19 pandemic, it was observed that giant cell arteritis (GCA) diagnoses increased at the Royal National Hospital for Rheumatic Diseases (RNHRD) in Bath, UK. This finding may support the viral aetiology hypothesis of GCA. Better understanding of the causes of GCA may help improve diagnostic and treatment strategies leading to better outcomes for patients., Objectives: The study aims to estimate the local incidence of GCA during the early COVID-19 pandemic (2020-2021) and compare it to pre-pandemic (2015-2019) data. This study will also evaluate the temporal relationship between COVID-19 infections and GCA diagnoses., Methods: Annual incidence rates of GCA were calculated between 2015 and 2021. Local COVID-19 prevalence was estimated by measuring the number of hospital beds taken up by COVID-19 positive patients. Poisson statistics were used to compare the annual mean incidence of GCA between 2019 and 2020, and Granger causality tested the temporal relationship between COVID-19 prevalence and GCA incidence., Results: There were 60 (95% confidence interval [CI] 46-77) GCA diagnoses made in 2020 compared to 28 (CI 19-41) in 2019 ( P = 0.016). Peaks in the number of COVID-19 inpatients correlated with peaks in GCA diagnoses. Granger causality testing found a statistically significant association between these peaks with a lag period of 40-45 days., Conclusion: The incidence of GCA in Bath was significantly increased in 2020 and 2021 compared to 2015-2019. The lag period between peaks was 40-45 days, suggesting that the COVID-19 virus may be a precipitating factor for GCA. More work is currently underway to interrogate the causal relationship between these two diseases., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (© 2023 The Authors.) more...
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- 2023
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37. Monoaminergic mediation of hyperalgesic and analgesic descending control of nociception in mice.
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Nemoto W, Kozak D, Sotocinal SG, Tansley S, Bannister K, and Mogil JS
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- Rats, Mice, Animals, Fluoxetine pharmacology, Fluoxetine therapeutic use, Serotonin, Reboxetine, Nociception, Rats, Sprague-Dawley, Analgesics, Norepinephrine physiology, Hyperalgesia drug therapy, Chronic Pain
- Abstract
Abstract: Descending control of nociception (DCN; also known as conditioned pain modulation [CPM], the behavioral correlate of diffuse noxious inhibitory controls) is the phenomenon whereby pain inhibits pain in another part of the body and is the subject of increasing study because it may represent a biomarker of chronic pain. We recently discovered that pain modulation on the application of a DCN paradigm involving low-intensity test stimuli occurs in the direction of hyperalgesia in healthy mice and rats, whereas the use of high-intensity stimuli produces analgesia. To elucidate the physiological mechanisms underlying hyperalgesic DCN, we administered agonists and antagonists of norepinephrine (NE) and serotonin (5-HT) receptors, key neurochemical players in the production of analgesic DCN. We find that 3 different monoamine reuptake inhibitors-the NE-selective reboxetine, the 5-HT-selective fluoxetine, and the dual NE/5-HT agonist duloxetine-all abolish hyperalgesic DCN when administered into the spinal cord (but not systemically), with no effect on heat or mechanical pain sensitivity. The reversal by reboxetine of hyperalgesic DCN is mediated by α 2 -adrenergic receptors (ie, blocked by atipamezole), and the fluoxetine reversal is mediated by 5-HT 7 receptors (ie, blocked by SB269970). By contrast, analgesic DCN was found to be reversed by atipamezole and SB269970 themselves, with no effect of reboxetine or fluoxetine. Thus, hyperalgesic DCN seems to be the neurochemical opposite to analgesic DCN. These data further validate and help elucidate a preclinical paradigm that mimics dysfunctional CPM and thus may form the basis of translational experiments that aim to reveal preventative pharmacological strategies for individuals predisposed to persistent pain., (Copyright © 2022 International Association for the Study of Pain.) more...
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- 2023
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38. Health outcomes of penicillin allergy testing in children: a systematic review.
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Kwok M, Heard KL, May A, Pilgrim R, Sandoe J, Tansley S, and Scott J
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- Humans, Child, Adolescent, Penicillins adverse effects, Anti-Bacterial Agents adverse effects, Outcome Assessment, Health Care, Drug Hypersensitivity diagnosis, Hypersensitivity drug therapy
- Abstract
Background: Penicillin allergy labels are commonly acquired in childhood and lead to avoidance of first-line penicillin antibiotics. Understanding the health outcomes of penicillin allergy testing (PAT) can strengthen its place in antimicrobial stewardship efforts., Objectives: To identify and summarize the health outcomes of PAT in children., Methods: Embase, MEDLINE, Web of Science, Cochrane Library, SCOPUS and CINAHL were searched from inception to 11 Oct 2021 (Embase and MEDLINE updated April 2022). Studies that utilized in vivo PAT in children (≤18 years old) and reported outcomes relevant to the study objectives were included., Results: Thirty-seven studies were included in the review, with a total of 8411 participants. The most commonly reported outcomes were delabelling, subsequent penicillin courses, and tolerability to penicillin courses. Ten studies had patient-reported tolerability to subsequent penicillin use, with a median 93.6% (IQR 90.3%-97.8%) of children tolerating a subsequent course of penicillins. In eight studies, a median 97.3% (IQR 96.4%-99.0%) of children were reported as 'delabelled' after a negative PAT without further definition. Three separate studies verified delabelling by checking electronic or primary care medical records, where 48.0%-68.3% children were delabelled. No studies reported on outcomes relating to disease burden such as antibiotic resistance, mortality, infection rates or cure rates., Conclusions: Safety and efficacy of PAT and subsequent penicillin use was the focus of existing literature. Further research is required to determine the long-term impact of delabelling penicillin allergies on disease burden., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.) more...
- Published
- 2023
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39. mTORC2 mediates structural plasticity in distal nociceptive endings that contributes to pain hypersensitivity following inflammation.
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Wong C, Barkai O, Wang F, Perez CT, Lev S, Cai W, Tansley S, Yousefpour N, Hooshmandi M, Lister KC, Latif M, Cuello AC, Prager-Khoutorsky M, Mogil JS, Séguéla P, De Koninck Y, Ribeiro-da-Silva A, Binshtok AM, and Khoutorsky A more...
- Subjects
- Humans, Hyperalgesia genetics, Hyperalgesia metabolism, Inflammation chemically induced, Inflammation genetics, Mechanistic Target of Rapamycin Complex 2 genetics, Mechanistic Target of Rapamycin Complex 2 metabolism, Rapamycin-Insensitive Companion of mTOR Protein genetics, Rapamycin-Insensitive Companion of mTOR Protein metabolism, Sirolimus, Chronic Pain, Nociceptors physiology
- Abstract
The encoding of noxious stimuli into action potential firing is largely mediated by nociceptive free nerve endings. Tissue inflammation, by changing the intrinsic properties of the nociceptive endings, leads to nociceptive hyperexcitability and thus to the development of inflammatory pain. Here, we showed that tissue inflammation-induced activation of the mammalian target of rapamycin complex 2 (mTORC2) triggers changes in the architecture of nociceptive terminals and leads to inflammatory pain. Pharmacological activation of mTORC2 induced elongation and branching of nociceptor peripheral endings and caused long-lasting pain hypersensitivity. Conversely, nociceptor-specific deletion of the mTORC2 regulatory protein rapamycin-insensitive companion of mTOR (Rictor) prevented inflammation-induced elongation and branching of cutaneous nociceptive fibers and attenuated inflammatory pain hypersensitivity. Computational modeling demonstrated that mTORC2-mediated structural changes in the nociceptive terminal tree are sufficient to increase the excitability of nociceptors. Targeting mTORC2 using a single injection of antisense oligonucleotide against Rictor provided long-lasting alleviation of inflammatory pain hypersensitivity. Collectively, we showed that tissue inflammation-induced activation of mTORC2 causes structural plasticity of nociceptive free nerve endings in the epidermis and inflammatory hyperalgesia, representing a therapeutic target for inflammatory pain. more...
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- 2022
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40. Microglia-mediated degradation of perineuronal nets promotes pain.
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Tansley S, Gu N, Guzmán AU, Cai W, Wong C, Lister KC, Muñoz-Pino E, Yousefpour N, Roome RB, Heal J, Wu N, Castonguay A, Lean G, Muir EM, Kania A, Prager-Khoutorsky M, Zhang J, Gkogkas CG, Fawcett JW, Diatchenko L, Ribeiro-da-Silva A, De Koninck Y, Mogil JS, and Khoutorsky A more...
- Subjects
- Animals, Extracellular Matrix pathology, Rats, Rats, Sprague-Dawley, Hyperalgesia etiology, Hyperalgesia pathology, Hyperalgesia physiopathology, Microglia pathology, Pain pathology, Pain physiopathology, Peripheral Nerve Injuries complications, Peripheral Nerve Injuries pathology, Spinal Cord Dorsal Horn pathology, Spinal Cord Dorsal Horn physiopathology
- Abstract
Activation of microglia in the spinal cord dorsal horn after peripheral nerve injury contributes to the development of pain hypersensitivity. How activated microglia selectively enhance the activity of spinal nociceptive circuits is not well understood. We discovered that after peripheral nerve injury, microglia degrade extracellular matrix structures, perineuronal nets (PNNs), in lamina I of the spinal cord dorsal horn. Lamina I PNNs selectively enwrap spinoparabrachial projection neurons, which integrate nociceptive information in the spinal cord and convey it to supraspinal brain regions to induce pain sensation. Degradation of PNNs by microglia enhances the activity of projection neurons and induces pain-related behaviors. Thus, nerve injury-induced degradation of PNNs is a mechanism by which microglia selectively augment the output of spinal nociceptive circuits and cause pain hypersensitivity. more...
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- 2022
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41. Long-term male-specific chronic pain via telomere- and p53‑mediated spinal cord cellular senescence.
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Muralidharan A, Sotocinal SG, Yousefpour N, Akkurt N, Lima LV, Tansley S, Parisien M, Wang C, Austin JS, Ham B, Dutra GM, Rousseau P, Maldonado-Bouchard S, Clark T, Rosen SF, Majeed MR, Silva O, Nejade R, Li X, Donayre Pimentel S, Nielsen CS, Neely GG, Autexier C, Diatchenko L, Ribeiro-da-Silva A, and Mogil JS more...
- Subjects
- Animals, Cellular Senescence, Female, Hyperalgesia metabolism, Male, Mice, Microglia metabolism, Spinal Cord metabolism, Telomere genetics, Telomere metabolism, Tumor Suppressor Protein p53 genetics, Tumor Suppressor Protein p53 metabolism, Chronic Pain genetics, Chronic Pain metabolism, Neuralgia genetics, Neuralgia metabolism
- Abstract
Mice with experimental nerve damage can display long‑lasting neuropathic pain behavior. We show here that 4 months and later after nerve injury, male but not female mice displayed telomere length (TL) reduction and p53‑mediated cellular senescence in the spinal cord, resulting in maintenance of pain and associated with decreased lifespan. Nerve injury increased the number of p53‑positive spinal cord neurons, astrocytes, and microglia, but only in microglia was the increase male‑specific, matching a robust sex specificity of TL reduction in this cell type, which has been previously implicated in male‑specific pain processing. Pain hypersensitivity was reversed by repeated intrathecal administration of a p53‑specific senolytic peptide, only in male mice and only many months after injury. Analysis of UK Biobank data revealed sex-specific relevance of this pathway in humans, featuring male‑specific genetic association of the human p53 locus (TP53) with chronic pain and a male-specific effect of chronic pain on mortality. Our findings demonstrate the existence of a biological mechanism maintaining pain behavior, at least in males, occurring much later than the time span of virtually all extant preclinical studies. more...
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- 2022
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42. Single-cell RNA sequencing reveals time- and sex-specific responses of mouse spinal cord microglia to peripheral nerve injury and links ApoE to chronic pain.
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Tansley S, Uttam S, Ureña Guzmán A, Yaqubi M, Pacis A, Parisien M, Deamond H, Wong C, Rabau O, Brown N, Haglund L, Ouellet J, Santaguida C, Ribeiro-da-Silva A, Tahmasebi S, Prager-Khoutorsky M, Ragoussis J, Zhang J, Salter MW, Diatchenko L, Healy LM, Mogil JS, and Khoutorsky A more...
- Subjects
- Animals, Cell Proliferation, Female, Gene Expression, Male, Mice, Mice, Inbred C57BL, Polymorphism, Genetic, Apolipoproteins E genetics, Chronic Pain genetics, Microglia, Peripheral Nerve Injuries, Sequence Analysis, RNA, Spinal Cord
- Abstract
Activation of microglia in the spinal cord following peripheral nerve injury is critical for the development of long-lasting pain hypersensitivity. However, it remains unclear whether distinct microglia subpopulations or states contribute to different stages of pain development and maintenance. Using single-cell RNA-sequencing, we show that peripheral nerve injury induces the generation of a male-specific inflammatory microglia subtype, and demonstrate increased proliferation of microglia in male as compared to female mice. We also show time- and sex-specific transcriptional changes in different microglial subpopulations following peripheral nerve injury. Apolipoprotein E (Apoe) is the top upregulated gene in spinal cord microglia at chronic time points after peripheral nerve injury in mice. Furthermore, polymorphisms in the APOE gene in humans are associated with chronic pain. Single-cell RNA sequencing analysis of human spinal cord microglia reveals a subpopulation with a disease-related transcriptional signature. Our data provide a detailed analysis of transcriptional states of mouse and human spinal cord microglia, and identify a link between ApoE and chronic pain in humans., (© 2022. The Author(s).) more...
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- 2022
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43. Corrigendum to: A systematic review and meta-analysis to inform cancer screening guidelines in idiopathic inflammatory myopathies.
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Oldroyd AGS, Allard AB, Callen JP, Chinoy H, Chung L, Fiorentino D, George MD, Gordon P, Kolstad K, Kurtzman DJB, Machado PM, McHugh NJ, Postolova A, Selva-O'Callaghan A, Schmidt J, Tansley S, Vleugels RA, Werth VP, and Aggarwal R more...
- Published
- 2021
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44. Anti-Cytosolic 5'-Nucleotidase 1A Autoantibodies Are Absent in Juvenile Dermatomyositis.
- Author
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Rietveld A, Wienke J, Visser E, Vree Egberts W, Schlumberger W, van Engelen B, van Royen-Kerkhof A, Lu H, Wedderburn L, Saris C, Tansley S, and Pruijn G
- Subjects
- Adolescent, Case-Control Studies, Child, Child, Preschool, Enzyme-Linked Immunosorbent Assay, Female, Humans, Immunoblotting, Male, 5'-Nucleotidase immunology, Autoantibodies immunology, Dermatomyositis immunology
- Abstract
Objective: To assess anti-cytosolic 5'-nucleotidase 1A (anti-cN-1A) autoantibodies in children with juvenile dermatomyositis (DM) and healthy controls, using 3 different methods of antibody detection, as well as verification of the results in an independent cohort., Methods: Anti-cN-1A reactivity was assessed in 34 Dutch juvenile DM patients and 20 healthy juvenile controls using the following methods: a commercially available full-length cN-1A enzyme-linked immunosorbent assay (ELISA), a synthetic peptide ELISA, and immunoblotting with a lysate from cN-1A-expressing HEK 293 cells. Sera from juvenile DM patients with active disease and those with disease in remission were analyzed. An independent British cohort of 110 juvenile DM patients and 43 healthy juvenile controls was assessed using an in-house full-length cN-1A ELISA., Results: Anti-cN-1A reactivity was not present in sera from juvenile DM patients or healthy controls when tested with the commercially available full-length cN-1A ELISA or by immunoblotting, in either active disease or disease in remission. Additionally, in the British juvenile DM cohort, anti-cN-1A reactivity was not detected. Three Dutch juvenile DM patients had weakly positive results for 1 of 3 synthetic cN-1A peptides measured by ELISA., Conclusion: Juvenile DM patients and young healthy individuals did not show anti-cN-1A reactivity as assessed by different antibody detection techniques., (© 2021 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.) more...
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- 2021
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45. A systematic review and meta-analysis to inform cancer screening guidelines in idiopathic inflammatory myopathies.
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Oldroyd AGS, Allard AB, Callen JP, Chinoy H, Chung L, Fiorentino D, George MD, Gordon P, Kolstad K, Kurtzman DJB, Machado PM, McHugh NJ, Postolova A, Selva-O'Callaghan A, Schmidt J, Tansley S, Vleugels RA, Werth VP, and Aggarwal R more...
- Subjects
- Adenosine Triphosphatases immunology, Age Factors, Antibodies, Antinuclear blood, Creatine Kinase blood, DNA-Binding Proteins immunology, Deglutition Disorders complications, Dermatomyositis complications, Dermatomyositis diagnosis, Dermatomyositis etiology, Female, Humans, L-Lactate Dehydrogenase blood, Lung Diseases, Interstitial complications, Male, Myositis blood, Neoplasms etiology, Publication Bias, Raynaud Disease complications, Risk, Sex Factors, Skin Ulcer complications, Tomography, X-Ray Computed, Transcription Factors immunology, Guidelines as Topic, Myositis complications, Neoplasms diagnosis
- Abstract
Objectives: To identify clinical factors associated with cancer risk in the idiopathic inflammatory myopathies (IIMs) and to systematically review the existing evidence related to cancer screening., Methods: A systematic literature search was carried out on Medline, Embase and Scopus. Cancer risk within the IIM population (i.e. not compared with the general population) was expressed as risk ratios (RR) for binary variables and weighted mean differences (WMD) for continuous variables. Evidence relating to cancer screening practices in the IIMs were synthesized via narrative review., Results: Sixty-nine studies were included in the meta-analysis. DM subtype (RR 2.21), older age (WMD 11.19), male sex (RR 1.53), dysphagia (RR 2.09), cutaneous ulceration (RR 2.73) and anti-transcriptional intermediary factor-1 gamma positivity (RR 4.66) were identified as being associated with significantly increased risk of cancer. PM (RR 0.49) and clinically amyopathic DM (RR 0.44) subtypes, Raynaud's phenomenon (RR 0.61), interstitial lung disease (RR 0.49), very high serum creatine kinase (WMD -1189.96) or lactate dehydrogenase (WMD -336.52) levels, and anti-Jo1 (RR 0.45) or anti-EJ (RR 0.17) positivity were identified as being associated with significantly reduced risk of cancer. Nine studies relating to IIM-specific cancer screening were included. CT scanning of the thorax, abdomen and pelvis appeared to be effective in identifying underlying asymptomatic cancers., Conclusion: Cancer risk factors should be evaluated in patients with IIM for risk stratification. Screening evidence is limited but CT scanning could be useful. Prospective studies and consensus guidelines are needed to establish cancer screening strategies in IIM patients., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology.) more...
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- 2021
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46. 4E-BP2-dependent translation in parvalbumin neurons controls epileptic seizure threshold.
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Sharma V, Sood R, Lou D, Hung TY, Lévesque M, Han Y, Levett JY, Wang P, Murthy S, Tansley S, Wang S, Siddiqui N, Tahmasebi S, Rosenblum K, Avoli M, Lacaille JC, Sonenberg N, and Khoutorsky A
- Subjects
- Animals, Class I Phosphatidylinositol 3-Kinases genetics, Class I Phosphatidylinositol 3-Kinases metabolism, Epilepsy genetics, Epilepsy physiopathology, Eukaryotic Initiation Factors genetics, Mechanistic Target of Rapamycin Complex 1 metabolism, Mice, Mice, Inbred C57BL, Neural Inhibition, Neurons physiology, Parvalbumins genetics, Parvalbumins metabolism, Epilepsy metabolism, Eukaryotic Initiation Factors metabolism, Neurons metabolism
- Abstract
The mechanistic/mammalian target of rapamycin complex 1 (mTORC1) integrates multiple signals to regulate critical cellular processes such as mRNA translation, lipid biogenesis, and autophagy. Germline and somatic mutations in mTOR and genes upstream of mTORC1, such as PTEN , TSC1/2 , AKT3 , PIK3CA , and components of GATOR1 and KICSTOR complexes, are associated with various epileptic disorders. Increased mTORC1 activity is linked to the pathophysiology of epilepsy in both humans and animal models, and mTORC1 inhibition suppresses epileptogenesis in humans with tuberous sclerosis and animal models with elevated mTORC1 activity. However, the role of mTORC1-dependent translation and the neuronal cell types mediating the effect of enhanced mTORC1 activity in seizures remain unknown. The eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) and 2 (4E-BP2) are translational repressors downstream of mTORC1. Here we show that the ablation of 4E-BP2, but not 4E-BP1, in mice increases the sensitivity to pentylenetetrazole (PTZ)- and kainic acid (KA)-induced seizures. We demonstrate that the deletion of 4E-BP2 in inhibitory, but not excitatory neurons, causes an increase in the susceptibility to PTZ-induced seizures. Moreover, mice lacking 4E-BP2 in parvalbumin, but not somatostatin or VIP inhibitory neurons exhibit a lowered threshold for seizure induction and reduced number of parvalbumin neurons. A mouse model harboring a human PIK3CA mutation that enhances the activity of the PI3K-AKT pathway ( Pik3ca
H1047R-Pvalb ) selectively in parvalbumin neurons shows susceptibility to PTZ-induced seizures. Our data identify 4E-BP2 as a regulator of epileptogenesis and highlight the central role of increased mTORC1-dependent translation in parvalbumin neurons in the pathophysiology of epilepsy., Competing Interests: The authors declare no competing interest. more...- Published
- 2021
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47. Increased number of cases of giant cell arteritis and higher rates of ophthalmic involvement during the era of COVID-19.
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Luther R, Skeoch S, Pauling JD, Curd C, Woodgate F, and Tansley S
- Abstract
Objectives: Our centre offers a fast-track assessment service for patients with suspected GCA and this service continued to operate during the coronavirus disease 2019 (COVID-19) pandemic. During and immediately following the peak of the COVID-19 pandemic in the UK we observed an increase in the number of patients diagnosed with GCA as well as an increased number of patients with visual complications. Our aim was to investigate this further., Methods: The electronic medical records of all patients referred for GCA fast-track assessment from January 2019 were reviewed. A complete list of patients undergoing temporal artery ultrasound and temporal artery biopsy for investigation of GCA dating back to 2015 was also available., Results: In the 12 week period between April and June 2020, 24 patients were diagnosed with GCA. Six (25%) had associated visual impairment. In contrast, during 2019, 28 new diagnoses of GCA were made in total and just 10% of patients suffered visual involvement. The number of patients diagnosed with GCA in April-June 2020 was nearly 5-fold that of the same time period the previous year. GCA diagnoses between April and June 2020 were supported by imaging (temporal artery ultrasound or CT-PET) in 72% of cases. We noted a higher proportion of male patients and a lower median age but no clear difference in the duration of symptoms prior to assessment., Conclusions: The reasons behind our observations remain unclear. However, our findings support the viral aetiopathogenesis hypothesis for GCA and demonstrate the importance of maintaining access to urgent rheumatology services during periods of healthcare disruption., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology.) more...
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- 2020
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48. Genome-wide association reveals contribution of MRAS to painful temporomandibular disorder in males.
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Smith SB, Parisien M, Bair E, Belfer I, Chabot-Doré AJ, Gris P, Khoury S, Tansley S, Torosyan Y, Zaykin DV, Bernhardt O, de Oliveira Serrano P, Gracely RH, Jain D, Järvelin MR, Kaste LM, Kerr KF, Kocher T, Lähdesmäki R, Laniado N, Laurie CC, Laurie CA, Männikkö M, Meloto CB, Nackley AG, Nelson SC, Pesonen P, Ribeiro-Dasilva MC, Rizzatti-Barbosa CM, Sanders AE, Schwahn C, Sipilä K, Sofer T, Teumer A, Mogil JS, Fillingim RB, Greenspan JD, Ohrbach R, Slade GD, Maixner W, and Diatchenko L more...
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Animals, Cohort Studies, Disease Models, Animal, Genetic Association Studies, Genome-Wide Association Study, Genotype, Humans, Male, Mice, Mice, Knockout, Middle Aged, RNA, Messenger metabolism, Young Adult, ras Proteins deficiency, Facial Pain etiology, Polymorphism, Single Nucleotide genetics, Temporomandibular Joint Disorders complications, Temporomandibular Joint Disorders genetics, ras Proteins genetics
- Abstract
Painful temporomandibular disorders (TMDs) are the leading cause of chronic orofacial pain, but its underlying molecular mechanisms remain obscure. Although many environmental factors have been associated with higher risk of developing painful TMD, family and twin studies support a heritable genetic component as well. We performed a genome-wide association study assuming an additive genetic model of TMD in a discovery cohort of 999 cases and 2031 TMD-free controls from the Orofacial Pain: Prospective Evaluation and Risk Assessment (OPPERA) study. Using logistic models adjusted for sex, age, enrollment site, and race, we identified 3 distinct loci that were significant in combined or sex-segregated analyses. A single-nucleotide polymorphism on chromosome 3 (rs13078961) was significantly associated with TMD in males only (odds ratio = 2.9, 95% confidence interval: 2.02-4.27, P = 2.2 × 10). This association was nominally replicated in a meta-analysis of 7 independent orofacial pain cohorts including 160,194 participants (odds ratio = 1.16, 95% confidence interval: 1.0-1.35, P = 2.3 × 10). Functional analysis in human dorsal root ganglia and blood indicated this variant is an expression quantitative trait locus, with the minor allele associated with decreased expression of the nearby muscle RAS oncogene homolog (MRAS) gene (beta = -0.51, P = 2.43 × 10). Male mice, but not female mice, with a null mutation of Mras displayed persistent mechanical allodynia in a model of inflammatory pain. Genetic and behavioral evidence support a novel mechanism by which genetically determined MRAS expression moderates the resiliency to chronic pain. This effect is male-specific and may contribute to the lower rates of painful TMD in men. more...
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- 2019
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49. Sensory Trick Frames: A New Device for Blepharospasm Patients.
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Lorenzano D, Tansley S, and Ezra DG
- Abstract
Objective: To determine whether the use of unique customized spectacles provided with modified side arms may be helpful in reducing benign essential blepharospasm (BEB) in patients describing periocular sensory tricks (ST)., Methods: A prospective descriptive study of patients with BEB with positive periocular or temporal region ST phenomenon response under the care of the Botox Clinic at Moorfields Eye Hospital, London, UK. Nine consecutive patients with BEB describing ST were recruited, and the disease frequency and severity were assessed with the Jankovic Rating Scale (JRS) and the Blepharospasm Disability Index (BSDI) before and after the use of the sensory trick frames (STF)., Results: A reduction in the score was noted in both severity (p = 0.0115) and frequency patterns (p = 0.0117) in the JRS in patients using the STF. A significant reduction of the BSDI score was also observed (p = 0.0314)., Conclusion: All the patients selected and fitted with the STF had a reduction in spasms and related symptoms. This new device may be helpful in some selected BEB patients who previously responded positively to periocular pressure alleviating maneuvers. more...
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- 2019
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50. Social propinquity in rodents as measured by tube cooccupancy differs between inbred and outbred genotypes.
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Tuttle AH, Tansley S, Dossett K, Tohyama S, Khoutorsky A, Maldonado-Bouchard S, Stein L, Gerstein L, Crawhall-Duk H, Pearl R, Sukosd M, Leger P, Hardt OM, Yachnin D, Austin JS, Chan CM, Pooters T, Groves I, Martin LJ, Sonenberg N, Gkogkas CG, and Mogil JS more...
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- Animals, Female, Genotype, Male, Mice, Mice, Inbred Strains, Rats, Sprague-Dawley, Stress, Psychological, Inbreeding, Social Behavior
- Abstract
Existing assays of social interaction are suboptimal, and none measures propinquity, the tendency of rodents to maintain close physical proximity. These assays are ubiquitously performed using inbred mouse strains and mutations placed on inbred genetic backgrounds. We developed the automatable tube cooccupancy test (TCOT) based on propinquity, the tendency of freely mobile rodents to maintain close physical proximity, and assessed TCOT behavior on a variety of genotypes and social and environmental conditions. In outbred mice and rats, familiarity determined willingness to cooccupy the tube, with siblings and/or cagemates of both sexes exhibiting higher cooccupancy behavior than strangers. Subsequent testing using multiple genotypes revealed that inbred strain siblings do not cooccupy at higher rates than strangers, in marked contrast to both outbred and rederived wild mice. Mutant mouse strains with "autistic-like" phenotypes ( Fmr1
-/y and Eif4e Ser209Ala) displayed significantly decreased cooccupancy., Competing Interests: The authors declare no conflict of interest. more...- Published
- 2017
- Full Text
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